ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.530C>T (p.Pro177Leu) (rs751477326)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000477631 SCV000545313 uncertain significance Li-Fraumeni syndrome 2018-10-19 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 177 of the TP53 protein (p.Pro177Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in the germline of an individual affected with breast cancer (PMID: 30287823) and has been reported as a somatic variant in various tumor samples (PMID: 19336573, 21118481, 17311302, 21232794, 19509155, 22551440, 26837699). ClinVar contains an entry for this variant (Variation ID:406583). This variant is located within the DNA binding domain of the TP53 protein (PMID: 17311302), where a high percentage of previously reported TP53 missense variants have been found (PMID: 17606709). Experimental studies have shown that this variant disrupts transcriptional activity in different yeast-based assays, and slightly reduces DNA binding activity in vitro, but does not inhibit wild-type TP53 function in a dominant manner (PMID: 9627118, 16861262, 12826609). In summary, this variant is a rare missense change that has been shown to affect protein function. In the absence of further supportive evidence, it has been classified as a Variant of Uncertain Significance.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000759377 SCV000888668 uncertain significance not provided 2018-02-24 criteria provided, single submitter clinical testing

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